Tanaka Y, Eda H, Fujimoto K, Tanaka T, Ishikawa T, Ishitsuka H
Department of Oncology and Immunology, Nippon Roche Research Center, Kanagawa, Japan.
Cancer Res. 1990 Aug 1;50(15):4528-32.
Murine colon 26 adenocarcinoma causes a progressive weight loss and physiological changes associated with cachexia when it grows to a certain size. By the use of this tumor model several types of cytostatics were examined for their ability to alleviate cachexia. Among them, 5'-deoxy-5-fluorouridine could reverse a progressive weight loss and improve hypoglycemia, hyperglucocorticism, and hepatic malfunctions, as well as inhibiting the tumor growth. Cyclophosphamide, nimustine, and 2'-deoxy-5-fluorouridine were only slightly effective in reversing the wasting, while 5-fluorouracil, tegafur, mitomycin C, cis-platinum, and doxorubicin were not active. Within 3 days after 5'-deoxy-5-fluorouridine was administered to cachectic mice with large tumor burdens, the wasting was immediately reversed even at doses in which there was increase or no significant reduction in tumor growth. These results indicate that the anticachectic activity of 5'-deoxy-5-fluorouridine is independent of its antiproliferative activity.
小鼠结肠26腺癌生长到一定大小时会导致体重逐渐减轻以及出现与恶病质相关的生理变化。利用该肿瘤模型检测了几种细胞抑制剂缓解恶病质的能力。其中，5'-脱氧-5-氟尿苷可逆转体重逐渐减轻的情况，改善低血糖、高糖皮质激素血症和肝功能障碍，同时抑制肿瘤生长。环磷酰胺、尼莫司汀和2'-脱氧-5-氟尿苷在逆转消瘦方面效果甚微，而5-氟尿嘧啶、替加氟、丝裂霉素C、顺铂和阿霉素则无活性。在给患有大肿瘤负荷的恶病质小鼠施用5'-脱氧-5-氟尿苷后的3天内，即使在肿瘤生长增加或无显著减少的剂量下，消瘦也会立即得到逆转。这些结果表明，5'-脱氧-5-氟尿苷的抗恶病质活性与其抗增殖活性无关。
